Relapsed Adult AMLPhase 1NCT03848754
Pracinostat and Gemtuzumab Ozogamicin (PraGO) in Patients With Relapsed/Refractory Acute Myeloid Leukemia
A Phase 1 study testing Gemtuzumab Ozogamicin 3 mg/m^2, Gemtuzumab Ozogamicin 2 mg/m^2 and Pracinostat - 45 mg in people with Relapsed Adult AML, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a prospective, single-center phase 1 clinical study aimed at determining the maximum-tolerated dose and safety of the combination of gemtuzumab ozogamicin (GO) and pracinostat (P) in patients with relapsed/refractory acute myeloid leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Adult AML
- What is being tested?
- Gemtuzumab Ozogamicin 3 mg/m^2, Gemtuzumab Ozogamicin 2 mg/m^2 and Pracinostat - 45 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2019to 5 May 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Morphologically documented AML or secondary AML [from prior conditions such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN)] or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
- Age ≥60 years, with relapsed/refractory AML to at least one line of therapy. Patients with antecedent MDS who progressed to AML while on hypomethylating agent therapy will also be eligible.
- Age 18-59 years with relapsed/refractory AML to at least two lines of intensive induction chemotherapy, or one line of therapy if deemed unsuitable for further intensive chemotherapy.
- Patients aged 18 years or older with relapsed AML after allogeneic hematopoietic cell transplantation, if deemed unsuitable for further intensive chemotherapy.
- Detectable CD33 expression on AML blasts confirmed by flow cytometry.
- Karnofsky performance status ≥ 60 (or Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) of 2 or less).
Show all 23Show fewer
- Adequate organ system function as outlined below:
- Total bilirubin ≤ 2 x upper limit of normal (ULN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
- Serum creatinine ≤ 2 or a serum creatinine clearance ≤ 1.5 x ULN.
- Baseline EKG with QT-interval corrected (QTcF) ≤ 450ms.
- Females should be using adequate contraception, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential. Male patient should avoid impregnating a female partner.
- It is not known what effects this treatment has on human pregnancy or development of the embryo or fetus. Therefore, female patients participating in this study should avoid becoming pregnant, and male patients should avoid impregnating a female partner. Non-sterilized female patients of reproductive age and male patients should use effective methods of contraception through defined periods during and after study treatment as specified below.
- Female patients must meet one of the following:
- Postmenopausal for at least one year before the screening visit, or
- Surgically sterile, or
- If they are of childbearing potential, agree to practice two effective methods of contraception from the time of signing of the informed consent form through three months after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, or
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation methods] and withdrawal are not acceptable contraception methods.)
- Male patients, even if surgically sterilized (i.e., status post vasectomy), must agree to one of the following:
- Practice effective barrier contraception during the entire study treatment period and through 90 days after the last study drug dose, OR
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
- Ability to understand a written informed consent document, and the willingness to sign it.
Who cannot join
- Acute promyelocytic leukemia (APL).
- Prior chemotherapy, radiotherapy, or investigative agent within 14 days, or within five half-lives of study entry.
- Subjects must have recovered from side effects of prior treatment.
- The use of hydroxyurea for leukoreduction prior to start of dosing is permitted.
- Hematopoietic Stem Cell Transplantation (HCT) within 60 days of enrollment, or evidence of veno-occlusive disease (VOD) at any time post-transplant, or active graft-versus-host disease requiring systemic immunosuppressive therapy.
- Life-threatening illness unrelated to AML, or any serious medical or psychiatric illness that could potentially interfere with participation in this study.
- Active and uncontrolled human immunodeficiency virus (HIV), or chronic Hepatitis B, or Hepatitis C.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Pracinostat in Combination With Gemtuzumab Ozogamicin (PraGO) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
This is a prospective, single-center phase 1 clinical study aimed at determining the maximum-tolerated dose and safety of the combination of gemtuzumab ozogamicin (GO) and pracinostat (P) in patients with relapsed/refractory acute myeloid leukemia.
Read the detailed description
Relapsed/Refractory AML (RR-AML) is a serious medical condition where overall less than 10% survive beyond five years. Among RR-AML patients ineligible for intensive chemotherapy, this problem is magnified, and survival is measured in months. Hence, there is an urgent need for more efficacious and tolerable therapies for RR-AML.
The majority of AML expresses the cluster of differentiation 33 (CD33) surface antigen. Gemtuzumab Ozogamicin (GO) is a recombinant, humanized anti-CD33 monoclonal antibody covalently attached to the cytotoxic antitumor antibiotic calicheamicin. GO binds to the CD33 antigen on AML cells forming a complex which is internalized, resulting in the intracellular delivery of calicheamicin. Calicheamicin then binds to DNA in the minor groove, inciting DNA double strand breaks and triggering cell death. GO was recently FDA approved for patients with AML who cannot tolerate intensive chemotherapy, and additionally received FDA approval in the RR-AML setting on the basis of a modest complete response (CR) rate of 26% [95% confidence interval (CI) 16-40%].
The investigators are studying whether the addition of the Histone deacetylase (HDAC) inhibitor pracinostat to GO is safe, and effective. HDACs plays important role in transcription regulation and in the pathogenesis of cancer. HDAC inhibitors induces histone hyperacetylation, resulting in an open chromatin structure and restore transcription of critically silenced genes. In AML, early clinical trials using single agent Pracinostat have demonstrated potential activity against the disease.
In the context of GO, the investigators hypothesize HDAC inhibition may potentially synergize with GO to improve response against AML. Through HDAC inhibition mediated histone unwinding, open chromatin could allow for increased DNA delivery of calicheamicin within AML blasts and increased apoptosis. Further, pre-clinical data suggests HDAC inhibition could also increase CD33 expression in myeloid leukemia cells, thereby allowing for increased GO binding to AML blasts. This is the basis for the combination of these agents.
- Conditions
- Relapsed Adult AML
- Being tested
- Gemtuzumab Ozogamicin 3 mg/m^2, Gemtuzumab Ozogamicin 2 mg/m^2, Pracinostat - 45 mg, Pracinostat - 60 mg
- Keywords
- acute myeloid leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemtuzumab Ozogamicin 3 mg/m^2Drug
Also called Mylotarg
GO 3 mg/m^2 on Day 1, 4, and 7
Maintenance: 2mg/m2 intravenous administration on day 1, in a 28-day cycle.
Gemtuzumab Ozogamicin 2 mg/m^2Drug
Also called Mylotarg
GO 2 mg/m^2 on Day 1 of a 28-day cycle.
Pracinostat - 45 mgDrug
Induction: 45mg administered orally 3 days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by 1 week of rest, in 28-day cycles.
Pracinostat - 60 mgDrug
Escalation: 60 mg administered orally three days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by one week of rest, in 28-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Pracinostat 45 mg with Gemtuzumab Ozogamicin | Experimental | * Gemtuzumab Ozogamicin Induction: GO 3 mg/m^2 on Day 1, 4, and 7
* Pracinostat Induction: 45 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles. We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is < 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD. Receives: Drug: Gemtuzumab Ozogamicin 3 mg/m^2; Drug: Pracinostat - 45 mg |
| Pracinostat 60 mg with Gemtuzumab Ozogamicin | Experimental | * Gemtuzumab Ozogamicin Induction: GO 3 mg/m^2 on Day 1, 4, and 7
* Pracinostat: 60 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles.
We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is < 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD. Receives: Drug: Gemtuzumab Ozogamicin 3 mg/m^2; Drug: Pracinostat - 60 mg |
| Gemtuzumab Ozogamicin Monotherapy Maintenance | Experimental | Response will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction.
**Gemtuzumab Ozogamicin Maintenance: 2 mg/m^2 intravenous administration on day 1, in a 28-day cycle. Receives: Drug: Gemtuzumab Ozogamicin 2 mg/m^2 |
| Pracinostat with Gemtuzumab Ozogamicin Maintenance | Experimental | Response will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction.
* Gemtuzumab Ozogamicin Maintenance: 2 mg/m^2 intravenous administration on day 1, in a 28-day cycle.
* Pracinostat Maintenance: (In addition to GO, only if induction dose escalation occurs) 45 mg orally 3 days a week with 48 hours between dosing, for three consecutive weeks, followed by 1 week of rest, in a 28-day cycle. Receives: Drug: Gemtuzumab Ozogamicin 2 mg/m^2; Drug: Pracinostat - 45 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of subjects experiencing a dose-limiting toxicity.
Maximum-tolerated (MTD) dose of pracinostat in combination with fixed dose GO induction will be determined by the 3+3 design rules. If there are no dose-limiting toxicities (DLTs) in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in three or six patients, the study will be placed on hold. If there is < 2 DLTs in the first three or six patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first three patients at 60mg, an additional three patients will be enrolled to ensure six patients are treated at the MTD.
Measured: First 28-day cycle
Secondary outcomes (6)
Number of subjects surviving at six months.
The number of subjects alive at six months.
Measured: 6 Months
Number of subjects progression free at 6 months.
Defined by the IWG.
Measured: 6 Months
The number of subjects with a complete response.
A complete response will be defined as bone marrow blasts <5% with absolute neutrophil count ≥1000/L and platelet ≥100,000/mL.
Measured: Day 28
The number of subjects with complete response with incomplete count recovery (CRi).
CRi is defined as CR without platelet recovery or neutrophil recovery. This will be defined as bone marrow blasts <5% with absolute neutrophil count <1000/μL OR platelet <100,000/μL.
Measured: Day 28
The number of subjects with partial remission (PR).
Partial remission (PR) is defined by a decrease of at 50% or more in the percentage of blasts to less than 25% in the bone marrow. and normalized blood counts ( ANC>1000, Platelets>100,000/ml).
Measured: Day 28
The number of subjects with morphologic leukemia-free state (MLFS).
MLFS is bone marrow blasts <5% with absolute neutrophil count <1000/μL AND platelet <100,000/μL.
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2019
- Study start24 May 2019
- Primary completion5 May 2021
- Study completion5 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Adult AMLStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sameem M. Abedin, MD, Medical College of Wisconsin
- Investigators
- Sameem Abedin, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03848754
- Sponsor's protocol ID
- PRO 33922
- Status last verified
- Jun 2022
- First submitted
- 19 Feb 2019
- Last updated
- 30 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pracinostat in Combination With Gemtuzumab Ozogamicin (PraGO) in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT03848754
- Acronym / sponsor ID
- PRO 33922
- Conditions
- Relapsed Adult AML
- Keywords
- acute myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 24 May 2019 (actual)
- Primary completion
- 5 May 2021 (actual)
- Study completion
- 5 May 2021 (actual)
- First posted
- 21 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective, single-center phase 1 clinical study aimed at determining the maximum-tolerated dose and safety of the combination of gemtuzumab ozogamicin (GO) and pracinostat (P) in patients with relapsed/refractory acute myeloid leukemia.
Detailed description
Relapsed/Refractory AML (RR-AML) is a serious medical condition where overall less than 10% survive beyond five years. Among RR-AML patients ineligible for intensive chemotherapy, this problem is magnified, and survival is measured in months. Hence, there is an urgent need for more efficacious and tolerable therapies for RR-AML.
The majority of AML expresses the cluster of differentiation 33 (CD33) surface antigen. Gemtuzumab Ozogamicin (GO) is a recombinant, humanized anti-CD33 monoclonal antibody covalently attached to the cytotoxic antitumor antibiotic calicheamicin. GO binds to the CD33 antigen on AML cells forming a complex which is internalized, resulting in the intracellular delivery of calicheamicin. Calicheamicin then binds to DNA in the minor groove, inciting DNA double strand breaks and triggering cell death. GO was recently FDA approved for patients with AML who cannot tolerate intensive chemotherapy, and additionally received FDA approval in the RR-AML setting on the basis of a modest complete response (CR) rate of 26% [95% confidence interval (CI) 16-40%].
The investigators are studying whether the addition of the Histone deacetylase (HDAC) inhibitor pracinostat to GO is safe, and effective. HDACs plays important role in transcription regulation and in the pathogenesis of cancer. HDAC inhibitors induces histone hyperacetylation, resulting in an open chromatin structure and restore transcription of critically silenced genes. In AML, early clinical trials using single agent Pracinostat have demonstrated potential activity against the disease.
In the context of GO, the investigators hypothesize HDAC inhibition may potentially synergize with GO to improve response against AML. Through HDAC inhibition mediated histone unwinding, open chromatin could allow for increased DNA delivery of calicheamicin within AML blasts and increased apoptosis. Further, pre-clinical data suggests HDAC inhibition could also increase CD33 expression in myeloid leukemia cells, thereby allowing for increased GO binding to AML blasts. This is the basis for the combination of these agents.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Pracinostat 45 mg with Gemtuzumab Ozogamicin | Experimental | Drug: Gemtuzumab Ozogamicin 3 mg/m^2, Drug: Pracinostat - 45 mg* Gemtuzumab Ozogamicin Induction: GO 3 mg/m^2 on Day 1, 4, and 7 * Pracinostat Induction: 45 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles. We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is < 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD. |
| Pracinostat 60 mg with Gemtuzumab Ozogamicin | Experimental | Drug: Gemtuzumab Ozogamicin 3 mg/m^2, Drug: Pracinostat - 60 mg* Gemtuzumab Ozogamicin Induction: GO 3 mg/m^2 on Day 1, 4, and 7 * Pracinostat: 60 mg administered orally 3 days a week with 48 hours between dosing for 3 consecutive weeks, followed by 1 week of rest, in 28-day cycles. We will utilize a 3+3 design to determine the safe dose of pracinostat in combination with fixed dose GO. If there are no DLTs in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in 3 or 6 patients, the study will be placed on hold. If there is < 2 DLTs in the first 3 or 6 patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first 3 patients at 60 mg, an additional 3 patients will be enrolled to ensure 6 patients are treated at the MTD. |
| Gemtuzumab Ozogamicin Monotherapy Maintenance | Experimental | Drug: Gemtuzumab Ozogamicin 2 mg/m^2Response will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction. **Gemtuzumab Ozogamicin Maintenance: 2 mg/m^2 intravenous administration on day 1, in a 28-day cycle. |
| Pracinostat with Gemtuzumab Ozogamicin Maintenance | Experimental | Drug: Gemtuzumab Ozogamicin 2 mg/m^2, Drug: Pracinostat - 45 mgResponse will be assessed through bone marrow biopsy on Day 28. Patients achieving at least a partial remission marrow will be offered up to 5 cycles of maintenance therapy. Maintenance should begin no later than 42 days after initial induction. * Gemtuzumab Ozogamicin Maintenance: 2 mg/m^2 intravenous administration on day 1, in a 28-day cycle. * Pracinostat Maintenance: (In addition to GO, only if induction dose escalation occurs) 45 mg orally 3 days a week with 48 hours between dosing, for three consecutive weeks, followed by 1 week of rest, in a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Morphologically documented AML or secondary AML [from prior conditions such as myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN)] or therapy related AML (t-AML), as defined by World Health Organization (WHO) criteria.
- Age ≥60 years, with relapsed/refractory AML to at least one line of therapy. Patients with antecedent MDS who progressed to AML while on hypomethylating agent therapy will also be eligible.
- Age 18-59 years with relapsed/refractory AML to at least two lines of intensive induction chemotherapy, or one line of therapy if deemed unsuitable for further intensive chemotherapy.
- Patients aged 18 years or older with relapsed AML after allogeneic hematopoietic cell transplantation, if deemed unsuitable for further intensive chemotherapy.
- Detectable CD33 expression on AML blasts confirmed by flow cytometry.
Key exclusion criteria (7 listed)
- Acute promyelocytic leukemia (APL).
- Prior chemotherapy, radiotherapy, or investigative agent within 14 days, or within five half-lives of study entry.
- Hematopoietic Stem Cell Transplantation (HCT) within 60 days of enrollment, or evidence of veno-occlusive disease (VOD) at any time post-transplant, or active graft-versus-host disease requiring systemic immunosuppressive therapy.
- Life-threatening illness unrelated to AML, or any serious medical or psychiatric illness that could potentially interfere with participation in this study.
- Active and uncontrolled human immunodeficiency virus (HIV), or chronic Hepatitis B, or Hepatitis C.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gemtuzumab Ozogamicin 3 mg/m^2Also: MylotargGO 3 mg/m^2 on Day 1, 4, and 7 Maintenance: 2mg/m2 intravenous administration on day 1, in a 28-day cycle. | Drug | Pracinostat 45 mg with Gemtuzumab Ozogamicin, Pracinostat 60 mg with Gemtuzumab Ozogamicin |
| Gemtuzumab Ozogamicin 2 mg/m^2Also: MylotargGO 2 mg/m^2 on Day 1 of a 28-day cycle. | Drug | Gemtuzumab Ozogamicin Monotherapy Maintenance, Pracinostat with Gemtuzumab Ozogamicin Maintenance |
| Pracinostat - 45 mgInduction: 45mg administered orally 3 days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by 1 week of rest, in 28-day cycles. | Drug | Pracinostat 45 mg with Gemtuzumab Ozogamicin, Pracinostat with Gemtuzumab Ozogamicin Maintenance |
| Pracinostat - 60 mgEscalation: 60 mg administered orally three days a week with 48 hours between dosing (e.g., Monday, Wednesday, and Friday) for three consecutive weeks, followed by one week of rest, in 28-day cycles. | Drug | Pracinostat 60 mg with Gemtuzumab Ozogamicin |
Primary outcome
The number of subjects experiencing a dose-limiting toxicity.
Time frame: First 28-day cycle
Maximum-tolerated (MTD) dose of pracinostat in combination with fixed dose GO induction will be determined by the 3+3 design rules. If there are no dose-limiting toxicities (DLTs) in the first three patients, the dose of pracinostat will be escalated to 60mg. Escalation to the next dose level will be done only after the third patient on the previous dose level has been observed for 28 days, and no DLTs were noticed. If there is 1 DLT, an additional 3 patients will be tested at same dose level. If there are ≥ 2 DLTs in three or six patients, the study will be placed on hold. If there is < 2 DLTs in the first three or six patients, the dose of pracinostat will be escalated to 60mg. If there are no DLTs in the first three patients at 60mg, an additional three patients will be enrolled to ensure six patients are treated at the MTD.
6 secondary outcomes
Number of subjects surviving at six months.
Time frame: 6 Months
Number of subjects progression free at 6 months.
Time frame: 6 Months
The number of subjects with a complete response.
Time frame: Day 28
The number of subjects with complete response with incomplete count recovery (CRi).
Time frame: Day 28
The number of subjects with partial remission (PR).
Time frame: Day 28
The number of subjects with morphologic leukemia-free state (MLFS).
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sameem Abedin, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Gemtuzumab Ozogamicin 3 mg/m^2, Gemtuzumab Ozogamicin 2 mg/m^2 and Pracinostat - 45 mg in people with Relapsed Adult AML, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of subjects experiencing a dose-limiting toxicity. (time frame: First 28-day cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jun 2022.